This project proposes to establish a Family Registry for Breast Cancer (FRBC) as part of an NCl-funded cooperative registry. The FRBC will be population-based (in the Greater San Francisco Bay Area), include many racial/ethnic minorities, and use a cost-efficient design to: 1) collect pedigree information, epidemiologic data, and biologic specimens from breast cancer cases with a family history of breast, ovarian and/or childhood cancers; 2) identify a population at high- risk for breast cancer that could be examined for inherited BRCA1 and p53 mutations, and facilitate cloning and analysis of other susceptibility genes; and 3) identify and obtain biologic specimens from Greater Bay Area families with Li-Fraumeni syndrome and a select subset of Dr. Li's established Li-Fraumeni families to broaden the resource for characterizing genetic susceptibility to breast cancer. Data included in the FRBC will be available to approved investigators to further genetic and translational research for breast cancer. Cases included in the FRBC will be identified by the Northern California Cancer Center's (NCCC) population-based Greater Bay Area Cancer Registry (GBACR), which covers six million residents. During a 3-year ascertainment period, 8047 female cases (< age65) and 78 male cases (< age 80), diagnosed from 1/1/95 through 12/31/97, will be identified. Cases will be asked to complete a brief screening questionnaire about their family history of cancer. Based on the reported cancer patterns of breast, ovarian and childhood cancers in their families, we will classify cases as "exceptional," "ordinary," or "sporadic" probands. "Exceptional" and a sample of "ordinary" probands (n=875), the groups reporting positive family histories, will be sent a family pedigree and a brief risk-factor questionnaire. A race-stratified sample of "exceptional" and "ordinary" probands who complete the questionnaires (N= 424) will be asked to provide a blood sample and access to archived tissue. Affected relatives of probands from these high-risk families whose diagnoses have been verified by review of pathology and medical records will be asked to complete a family pedigree, donate blood, and provide access to archived tissue (N=648). Blood collected as part of the FRBC will be processed and stored at NCCC. Archived tissue will be prepared for storage by a Co- Investigator at Stanford University. With the proposed sampling strategy, racial/ethnic minorities will comprise one-half of the high-risk probands and affected family members. Cases will be followed using GBACR methods to obtain survival and recurrence data. Genetic counseling will be provided as needed using trained oncology nurse/genetic counselor pairs and existing community resources. An Operations Core will track all aspects of the project, record pedigrees, and make FRBC data accessible electronically; this unit also will conduct quality-control measures at all steps of data collection. Four pilot studies using the FRBC are proposed. FRBC Investigators will serve on NCl's Steering Committee and develop common policies for quality and distribution of data from the FRBC.